Nuclear Magnetic Resonance, or NMR, has been used for many years as a means of chemical analysis. NMR is a type of radio frequency spectroscopy which is based upon small energy differences between electrically charged atomic nuclei which are spinning parallel or antiparallel to an applied magnetic field. When radiofrequency energy is applied to the sample, these spinning atomic nuclei change spin states and, in doing so, absorb some of the radiofrequency energy. Nuclei in slightly different chemical environments within the same molecule change spin state at slightly different energies, and this produces the characteristic absorption or resonances which help identify the molecular structure.
NMR has more recently been used for spectroscopy and imaging examinations of the human body, and in this form is now often called MRI (Magnetic Resonance Imaging). Other methods, such as computerized axial tomography (CAT scanning), have been used in the past for this purpose, and still are. However, because NMR does not use ionizing radiation, it is believed to have some safety advantages over CAT scanning. In addition, NMR can detect chemical information whereas other techniques of imaging, such as ultrasound and X-rays, can only detect differences in the density of materials, Thus, NMR is an advantageous method for producing cross-sectional images of the human body.
Historically, nuclear magnetic resonance has been used for ex vivo studies of cells or tissues, or for in vivo observation of a living body. Generally, information can be obtained from the whole body or from a specified area of the body beneath the skin surface by application of a nuclear resonance phenomenon.
In one such method, described in Abe, U.S. Pat. No. 4,240,439, a method is provided for endoscopy of a specified area of a living body for obtaining high-resolution information on liquids such as intracellular or extracellular fluid, tumors such as benign or malignant tumors, inflammatory tissues, etc., through the medium of an NMR signal of a nuclear magnetic substance such as a proton, fluorine, magnesium, phosphorus, sodium, calcium, or the like, in an organ close to the surface of the skin, such as a mammary gland or the thyroid gland, a tubular or cavitary organ such as the uterus, an intestine, or the throat, or an organ incised by a surgical operation.
In traditional methods of studying pathology of organs, an abnormality of the organ target area is recognized merely as a shadow, and the qualitative judgement as to whether the abnormality is benign or malignant is finally made after a histomorphological examination. The same may be said of ultrasound measurements. The method of obtaining internal information of a target body from the outside thereof by the application of nuclear magnetic resonance techniques has a great advantage as a non-invasive method. NMR images contain chemical information in addition to morphological information, which can provide physiologic information.
The relaxation properties of water .sup.1 H nuclei are the basis for most of the contrast obtained by NMR imaging techniques. Conventional .sup.1 NMR images of biological tissues usually reflect a combination of spin-lattice (T.sub.1) and spin-spin (T.sub.2) water .sup.1 H relaxation. The variations in water .sup.1 H relaxation rate generate image contrast between different tissues and pathologies depending on how the NMR image is collected. The precise nature of the relaxation process in tissues is still an active area of research. It has been proposed that a predominant relaxation mechanism in biological tissues is cross-relaxation and/or chemical exchange between .sup.1 H in "free" or highly mobile water and .sup.1 H associated with macromolecules or immobile water (cf. Edzes et al., Nature (London) 265: 521 (1977); Edzes et al., J. Magn. Res. 31:207 (1978); Sobol et al., Biophys. J. 50: 181 (1986); Koenig, in Water in Polymers, Rowand, SP (ed), American Chemical Society, Washington, D.C. (1980), p. 157; Koenig et al. in NMR Spectroscopy of Cells and Organisms Vol. 2, R. K. Gupta (ed) CRC Press, Inc. Boca Raton, Fla. p. 75 (1987). These conclusions were based on detailed studies of the effect of static magnetic field strength as well as selective and non-selective excitation pulses on water .sup.1 H relaxation rates.
Understanding water .sup.1 H magnetization relaxation and exchange in biological tissues is important in the evaluation of the "state" of water in tissues as well as in the interpretation of NMR images for clinical studies.
Current technology possesses the technique of saturation transfer for both 31P and .sup.1 H NMR, but all studies to date have been one dimensional. .sup.1 H NMR imaging (MRI) is a technique that has been available for years, but images to date have all relied upon differences in T.sub.1, T.sub.2, or proton density for information about the sample being studied. These techniques, saturation transfer and NMR imaging, have never before been combined to permit the imaging of chemical exchange rates and proton metabolite concentrations.